The role of the intracellular ‘C3 system’ in cancer
The intracellular C3a/C3aR interaction contributes to basic processes of the cell, including normal proliferation via the mTOR/glycolysis axis. As pathological increased intracellular C3 activation contributes to abnormal cellular function in T cells and induces Th1 hyperactivity that contributes to autoimmunity, we argue that dysregulation of this system will likely also contribute to cancer (prostate cancer).
Surprisingly, while we observe ‘homeostatic’ C3a expression as expected within benign epithelial prostate cells, prostate cancer cells exhibit either little or no C3/C3a expression. Further, levels of reduction in C3a correlate significantly with higher Gleason scores (n=25) and – via modulation of tis intracellular C3 system – we can regulate cell proliferation in benign as well as malignantly transformed prostate cancer cell lines in vitro and in vivo. We are currently defining how exactly intracellular C3 regulates the maintenance of normal epithalial cell growth.